We propose a Neurotrauma Clinical Research Center at the University of Miami/Jackson Memorial Hospital Medical Center. The Program consists of five projects in clinical and basic science, and a Clinical Epidemiology and Biostatistics Core, whose primary aims are to create a comprehensive patient registry; to develop and implement prognostic indicators of mortality/morbidity and outcome; and to provide ongoing support to present and future projects. The Projects are unified by their concern with potentially treatable or preventable pathomechanisms of traumatic CNS injury. The role of brain temperature in modulating post-traumatic CNS injury is a particular area of common concern. Program areas include: (a) the clinical evaluation of altered brain temperature in patients with severe acute head injury, analyzing the significance of brain hyperthermia in relation to altered intracranial pressure, CSF metabolites, and clinical outcome; (b) hippocampal dysfunction following fluid-percussion head injury in the rat, integrating electrophysiological, neurotransmitter, and behavioral measures; (c) an analysis of post-traumatic microvascular integrity, blood-brain barrier, and cortical circuit function in the head- injured rat in relation to altered brain temperature; (d) mechanisms of injury-induced acute astrocytic swelling, with a focus on calcium and calcium-dependent kinases; and (e) the therapeutic role of moderate hypothermia in experimental contusive spinal cord injury. Our program relies upon several unique and outstanding institutional resources a) a 1485-bed university-centered major medical center which receives the overwhelming majority of head-injury and spinal cord-injury cases in Dade County, with its 2 million population; b) a newly restructured Department of Epidemiology and Public Health with expertise in data registries and trial design; and c) major ongoing research programs in both cerebral metabolism/ischemic cerebrovascular disease and in spinal cord injury, providing breadth and depth of multidisciplinary collaborative expertise.